ULTRA-SENSITIVE GRAPHENE NANO-BIOSENSORS

Abstract

Illnesses like cancer, cardiovascular diseases, Alzheimer's, Parkinson's, and diabetes have negative effects on patients, society and insurance systems. The ever-ageing population has a critical demand for more efficient, affordable healthcare.Nanotechnology is building nanometre sized devices for electronics and medical applications, raising expectations for better diagnostics and 'smart' treatments. Nanosensors could identify disease biomarkers at the earliest possible stage, potentially intercepting more serious illness. Available therapeutic options informed by early detection are greatly enhanced e.g. prostate cancer, the 2nd largest killer of male cancer patients, better than 70% chance of successful treatment if detected early. Biomarkers are often present at very low concentrations. Monitoring of biomarkers like prostate-specific-antigen, glucose or other blood-based markers at clinical concentrations - possible using nano-sensor arrays - could provide genuine benefits to patients. Non-invasive smart-testing using urine or breath samples would have a hugely beneficial impact on chronic patients and for monitoring biomarker levels after treatment. Current diagnosis of disease biomarkers is based on detection of fluorescently labeled probe molecules which interact with specific substrate-bound receptors. This is expensive and time-consuming, with limited sensitivity. Nanoscale electrochemical biosensors can achieve much higher sensitivities, using label-free biomarkers. We will exploit our recent advances in graphene growth and semiconductor surface functionalisation, to develop wafer-based, graphene/Silicon Carbide (SiC) technology for novel biosensor applications. Graphene, a single atomic layer of graphite, has some exceptional electronic properties such as its zero bandgap and very high carrier mobilities at room temperature - similar to carbon nanotubes. Graphene can be grown on SiC substrates using silicon sublimation. The principal advantage of graphene/SiC over conventional graphene - from exfoliation of graphene flakes from graphite substrates - is the capacity for graphene growth on flat, large-area wafers (up to 100mm in diameter), on which devices can subsequently be fabricated using standard semiconductor processing. Nano-channel graphene electronic devices will be fabricated on SiC substrates. We have shown that graphene can be bio-functionalized and will use surface functionalisation chemistry to attach bio-receptors to nano-channel graphene devices. Because of their high surface/volume ratio and quantum confinement properties, the electrical properties of graphene nano-channels have increased signal/noise ratios and are strongly influenced by minor perturbations, enabling biomarker detection at ultra-sensitive (fM) analyte levels. Current transport through the nanosensor should show extreme sensitivity to its local environment.A proof-of-concept nano-channel bio-sensor will be developed using antibody-functionalized graphene, capable of specific and selective interaction with the target prostate cancer biomarker, 8-hydroxydeoxyguanosine (8-OHdG). When the bio-molecule binds to the functionalised surface, it produces an electrical signal, which can be detected. The key to an effective biosensor is that only specific bio-molecules will bind to the receptor and produce a response. Selectivity can be controlled by choosing the correct bio-receptor.The functionalisation chemistry proposed allows for attachment of a variety of antibody, enzyme, or aminoacid bio-receptors. Our graphene/SiC biochip could eventually provide an ultra-sensitive, fast-diagnosis, cost-effective test for numerous disease biomarkers - potentially revolutionizing healthcare by bringing diagnosis and monitoring to the point-of-care. Once trialed, mobile monitoring systems, transmitting a signal to a hand held readout display, could allow translation of healthcare from hospitals to patients in their own homes.

Planned Impact

Nano-biosensors will provide early detection and diagnosis of disease, and enable real-time monitoring of patient's conditions with less invasive and more user-friendly technology - benefitting their quality of life. We will lay the foundations for a generic, ultrasensitive, biosensor technology that can be adapted to selectively and specifically detect numerous biomarkers - depending on the bio-receptor attached to the Graphene/Silicon Carbide device. Novel biosensor technology, validated for detection of a prostate cancer marker, could be used to functionalise discrete arrays of nanochannel devices for multiplexed sensing of a variety of biomarkers for real-time monitoring of multiple diseases. The flagship cross-disciplinary project will engage with academics and clinicians from across Swansea's Centre for Nanohealth (CNH) and with other universities to develop nanotechnology-based diagnostics for: diabetes, cancer, cardiovascular diseases, arthritis, and reproductive medicine, ensuring feedback between the sensor development team and clinical end-users. Dissemination of the sensor capabilities and communication with industry, academia, government agencies and the NHS will be essential to the eventual uptake of biosensor technology by the health service. The project will enable Dr. Guy to develop a world-class research group at Swansea and act as a springboard for new international collaborative research, building on links with Rice, Houston, CNM Barcelona, Linkoping, RPI, Catania, Bologna, STFC, and SOLEIL. Joint proposals developing biosensors for specific medical applications and integrating sensors with signal processing, display electronics, sampling, microfluidics and therapeutics. Integrated, miniaturized, hand-held, user-friendly, biosensor detection systems, could be used in a cost-effective hand-held POC device for reliable, real-time data capture for clinical analysis and interpretation. Once trialled clinically, mobile monitoring systems could eventually be used for Patient Self Assessment (PSA). At risk patients or patients undergoing or having undergone medical therapies or treatment could monitor themselves for disease biomarkers via non-invasive using urine or breath tests, significantly improving their quality of life. Biosensors have huge potential for innovation and intellectual property (IP) creation. The UK has several world class pharmaceutical and biotechnology companies that would benefit from the ultrasensitive, label-free detection system proposed. Industry is already geared up to market biochip technology, and Swansea University would work closely with industrial partners to exploit and commercialize the technology and IP developed. There are huge market applications for biosensor diagnostics in diabetes, cardiovascular disease and cancer treatments. The medical device market was 145 billion Euros in 2003, with in-vitro diagnostics representing 18 billion Euros. Nanotechnology will have a big impact on this expanding market in the coming years, offering faster and more accurate analyses of smaller samples and the potential for implantable devices - a paradigm shift in healthcare. Dr. Guy is in discussions with several major companies and small & medium sized enterprises including: pharmaceutical company UCB; Boots Centre for Innovation BCI; 3M; MicroPharm, Applied Nano Detectors (AND), Surface Technology Systems (STS) and SEAS Nanosolutions, regarding the commercial development of nano-biosensor technology. As well as the medical diagnostics and pharmaceutical markets, there are commercial opportunities in sensors for pathogens, hazardous chemical and biological agents and in agriculture. Following development of proof of concept devices, we will hold discussions on formal collaboration and licensing agreements. Dr. Guy has a strong track record of industrial engagement and knowledge transfer will aggressively exploit the technologies resulting from these projects.

Plymouth works towards characterising the graphene sensors and working towards identifying the blood based dementia biomarkers etc.

Impact

Resaerch articles, point of care graphene sensor

Start Year

2015

Description

Graphene collaboration with Cardiff University

Organisation

Cardiff University

Department

School of Chemistry

Country

United Kingdom

Sector

Academic/University

PI Contribution

We are working closely with Prof. Phil Davies form cardiff University and this has resulted in an NRN project. Currently we are working on a resaerch funding bid to Leverhulme Trust.

Collaborator Contribution

Parrtner support the surface characterisation on graphene and collaboratively contribute to the proposal development and preparation.

Impact

This multi-diciplinary collaboration resulted in a PhD fudned project supported by NRN Intiations. Presently we are developing a funding bid to Leverhulme Trust.

Start Year

2012

Description

Industry collaborations with IQE

Organisation

IQE Europe Limited

Country

United Kingdom

Sector

Private

PI Contribution

Collaborations on semiconductor fabrication technologies

Collaborator Contribution

Semiconductor wafer supply and optimisation

Impact

Silicon microneedles were fabricated

Start Year

2016

Description

Industry collaborations with Newport Wafer Fab Ltd

Organisation

Newport Wafer Fab Ltd

PI Contribution

Developing semiconductor technology processes

Collaborator Contribution

wafer supply

Impact

Silicon microneedles

Start Year

2016

Title

A method of making a semiconductor wafer

Description

The invention related to a semiconducting wafer and a method of making a semiconductor wafer. In a method of making a semiconducting wafer, the method comprises forming a trench 26 in a single crystal wafer substrate 10, anisotropically etching in the trench 26 to form a notch 28, 30 and using the notch 28, 30 as an initiation site to split the substrate 10 along a crystal plane to separate a slim wafer 12.

IP Reference

GB2489397

Protection

Patent granted

Year Protection Granted

2012

Licensed

Yes

Impact

Developed a new method of making a semiconductor wafer.

Title

Splitting of Nanosheets

Description

Developed the process of splitting the nanosheets

IP Reference

P100029GB

Protection

Patent granted

Year Protection Granted

2015

Licensed

Commercial In Confidence

Impact

Process development resulting isjoint collabortive research projects

Description

Bath Electrochemical Impedance Spectroscopy Summer School 2016

Form Of Engagement Activity

Participation in an activity, workshop or similar

Part Of Official Scheme?

No

Geographic Reach

International

Primary Audience

Postgraduate students

Results and Impact

One of the post doc, Dr. Anitha Devadoss, attended the Bath Electrochemical Impedance Spectroscopy Summer School 2016 during 12-15th July 2016

Biosense Dementia 2017 workshop was arranged by Plymouth university in June 2017. Ryan Bigham, PhD student from prof. Owen's group has attended the devent and presented a poster entitled "Graphene based biosensor for detection of dementia biomakers" and won the best poster prize!

International women in Engineering 2017 event is organised within Swansea University to showcase the Successful women in Engineering discipline. Dr. Anitha Devadoss, presented her international work experinece to the graduate/postgraduate/early career researchers.

Dr. Anitha Devadoss presented an invited talk on "Nanomaterial Platforms and Signal Amplification Strategies for Biosensors" at Vellore Institute of Technology University, on 14th August 2017. More than 50 Undergraduyate/post graduate resaerch students participated in this talk. New collaborations with VIT University were developed.

Year(s) Of Engagement Activity

2017

Description

Invited talk at 7th Innovation Academy Symposium

Form Of Engagement Activity

A talk or presentation

Part Of Official Scheme?

No

Geographic Reach

National

Primary Audience

Postgraduate students

Results and Impact

Delivered an invited talk in London at 7th Innovation Academy Symposium.

Year(s) Of Engagement Activity

2017

Description

Invited talk at Advances in Companion Diagnostics, London

Form Of Engagement Activity

A talk or presentation

Part Of Official Scheme?

No

Geographic Reach

National

Primary Audience

Postgraduate students

Results and Impact

Preseanted an invited talk on graphene biosnesors

Year(s) Of Engagement Activity

2017

Description

Invited talk at CoInnovate

Form Of Engagement Activity

A talk or presentation

Part Of Official Scheme?

No

Geographic Reach

National

Primary Audience

Industry/Business

Results and Impact

Delivered an invited talk at the coinnovate event organised by Ser Cymru NRN at Cardiff on 24/01/2018

Year(s) Of Engagement Activity

2018

Description

Invited talk at CoInnovate, Cardiff

Form Of Engagement Activity

A talk or presentation

Part Of Official Scheme?

No

Geographic Reach

National

Primary Audience

Industry/Business

Results and Impact

Delivered an invited talk on advances in engineering technologies for healthcare applications

Year(s) Of Engagement Activity

2017

Description

Invited talk at Pfizer visit to Swansea University

Form Of Engagement Activity

Participation in an activity, workshop or similar

Part Of Official Scheme?

No

Geographic Reach

Local

Primary Audience

Professional Practitioners

Results and Impact

Senior managemnet team from Pfizer visited Swansea University. we have represented the Medical Devices research team within Swansea university and future collaborations were discussed.

PhD studnet, Ryan Bigham has attended the "NRN Ser Cymru post graduate research conference 2017" in September 2017 and presented a poster at the conference on Graphene Biosesors, displaying his PhD work.

Year(s) Of Engagement Activity

2017

Description

NRN end of year general meeting

Form Of Engagement Activity

Participation in an activity, workshop or similar

Part Of Official Scheme?

No

Geographic Reach

National

Primary Audience

Postgraduate students

Results and Impact

Student Ryan Bigham attended the NRN end of year general meeting in Bay campus, swansea university.

Year(s) Of Engagement Activity

2016

Description

Nanotech France 2015

Form Of Engagement Activity

A talk or presentation

Part Of Official Scheme?

No

Geographic Reach

International

Primary Audience

Postgraduate students

Results and Impact

Nanotech France 2015 - A student has given the oral presentation of graphene biosensors

Prof. Owen guy attended an interview on their recent funding bid to SBRi in London

Year(s) Of Engagement Activity

2016

Description

Swansea - Hosted Marie Cure ITN workshop

Form Of Engagement Activity

Participation in an activity, workshop or similar

Part Of Official Scheme?

No

Geographic Reach

International

Primary Audience

Postgraduate students

Results and Impact

Swansea Univerity Hosted the Marie Cure ITN workshop for the early career resaerchers from our recently wonn marie curie network

Year(s) Of Engagement Activity

2017

Description

Swansea Science Festival 2017

Form Of Engagement Activity

Participation in an activity, workshop or similar

Part Of Official Scheme?

No

Geographic Reach

Regional

Primary Audience

Public/other audiences

Results and Impact

Swansea Science Festival 2017 event was held at National waterfront Museum between September 9-11 2017. A stall was displayed at the event demonstrating the biosensors research activity within Swansea University. Our entire group was involved in this and the event was a grand success . General public, children and graduate students attended the event.

Dr. Anitha Devadoss participated in the UK-Turkey Workshop "Electrochemical nucleic acid based biosensors / microfluidic devices for healthcare applications" organised by University of Bath during 5-8 September 2016. She delivered a oral presentation and a posted presentation during this event.